AR090994A1 - BICYCLICALLY REPLACED URACILES AND USE OF THE SAME - Google Patents
BICYCLICALLY REPLACED URACILES AND USE OF THE SAMEInfo
- Publication number
- AR090994A1 AR090994A1 ARP130101600A ARP130101600A AR090994A1 AR 090994 A1 AR090994 A1 AR 090994A1 AR P130101600 A ARP130101600 A AR P130101600A AR P130101600 A ARP130101600 A AR P130101600A AR 090994 A1 AR090994 A1 AR 090994A1
- Authority
- AR
- Argentina
- Prior art keywords
- alkyl
- hydrogen
- halogen
- difluoromethyl
- trifluoromethyl
- Prior art date
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/536—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines ortho- or peri-condensed with carbocyclic ring systems
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/538—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with carbocyclic ring systems
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Abstract
La presente solicitud se refiere a derivados de uracilo sustituidos bicíclicamente, a procedimientos de preparación de los mismos, al uso de los mismos solos o en combinaciones para el tratamiento y/o la prevención de enfermedades y al uso de los mismos para la producción de medicamentos para el tratamiento y/o la prevención de enfermedades. Reivindicación 1: Compuesto de la fórmula (1) en la que R¹ es hidrógeno o alquilo C₁₋₄; R² es un grupo de la fórmula (2), (3) ó (4) en la que * es el sitio de unión al átomo de nitrógeno del uracilo; A es -CH₂-, -CH₂-CH₂-, -O-CH₂-## u oxígeno, en el que ## es el sitio de unión al anillo de fenilo; m es el número 0, 1 ó 2; R⁴ es halógeno, difluorometilo, trifluorometilo, alquilo C₁₋₄, difluorometoxi, trifluorometoxi o alcoxi C₁₋₄; R⁵A es hidrógeno o deuterio; R⁵B es hidrógeno, deuterio o alquilo C₁₋₄; R⁶ es hidrógeno o flúor; R⁷ es hidrógeno o flúor; R⁸ es halógeno, difluorometilo, trifluorometilo, alquilo C₁₋₄ o nitro; R⁹ es hidrógeno, halógeno, difluorometilo, trifluorometilo, alquilo C₁₋₄, nitro o alquil C₁₋₄-tio; R³ es un grupo de la fórmula (5) en la que # es el sitio de unión al átomo de nitrógeno del uracilo; el anillo Q es heterociclo de 5 a 7 miembros o heteroarilo de 5 ó 6 miembros, en el que el heterociclo de 5 a 7 miembros o el heteroarilo de 5 ó 6 miembros puede estar sustituido con 1 a 4 sustituyentes seleccionados independientemente del grupo de halógeno, difluorometilo, trifluorometilo, trideuterometilo, alquilo C₁₋₆, cicloalquilo C₃₋₇, oxo, hidroxilo, alquil C₁₋₄-carbonilo, alcoxi C₁₋₄-carbonilo, aminocarbonilo y alquil C₁₋₄-sulfonilo, en el que el alquilo C₁₋₆ y el cicloalquilo C₃₋₇, ₐ ₛᵘ ᵛₑᶻ, ₚᵘₑᵈₑₙ ₑₛₜₐʳ ₛᵘₛₜⁱₜᵘⁱᵈₒₛ ᶜₒₙ ₁ ₐ ₃ ₛᵘₛₜⁱₜᵘʸₑₙₜₑₛ ₛₑₗₑᶜᶜⁱₒₙₐᵈₒₛ ⁱₙᵈₑₚₑₙᵈⁱₑₙₜₑₘₑₙₜₑ ᵈₑₗ ᵍʳᵘₚₒ ᵈₑ ₕₐₗóᵍₑₙₒ, ᶜⁱₐₙₒ, ₜʳⁱᶠₗᵘₒʳₒₘₑₜⁱₗₒ, ᶜⁱᶜₗₒₐₗqᵘⁱₗₒ C₃₋₇, hidroxilo, alcoxi C₁₋₄ y heterociclo de 4 a 7 miembros, y en el que dos radicales alquilo C₁₋₆ unidos a un átomo de carbono del heterociclo de 5 a 7 miembros y el heteroarilo de 5 ó 6 miembros, junto con el átomo de carbono al que están unidos, pueden formar un carbociclo de 3 a 6 miembros; R²⁴ es halógeno, alquilo C₁₋₄ o alcoxi C₁₋₄; n es el número 0, 1, 2 ó 3; y las sales, solvatos y solvatos de las sales del mismo.The present application refers to bicyclic substituted uracil derivatives, their preparation procedures, their use alone or in combinations for the treatment and / or prevention of diseases and their use for the production of medicines. for the treatment and / or prevention of diseases. Claim 1: Compound of the formula (1) wherein R¹ is hydrogen or C₁₋₄ alkyl; R² is a group of the formula (2), (3) or (4) in which * is the binding site to the uracil nitrogen atom; A is -CH₂-, -CH₂-CH₂-, -O-CH₂ - ## or oxygen, in which ## is the phenyl ring binding site; m is the number 0, 1 or 2; R⁴ is halogen, difluoromethyl, trifluoromethyl, C₁₋₄ alkyl, difluoromethoxy, trifluoromethoxy or C₁₋₄ alkoxy; R⁵A is hydrogen or deuterium; R⁵B is hydrogen, deuterium or C₁₋₄ alkyl; R⁶ is hydrogen or fluorine; R⁷ is hydrogen or fluorine; R⁸ is halogen, difluoromethyl, trifluoromethyl, C₁₋₄ alkyl or nitro; R⁹ is hydrogen, halogen, difluoromethyl, trifluoromethyl, C₁₋₄ alkyl, nitro or C₁₋₄-thio alkyl; R³ is a group of the formula (5) in which # is the binding site to the uracil nitrogen atom; the Q ring is 5-7 membered heterocycle or 5-6 membered heteroaryl, in which the 5-7 membered heterocycle or the 5- or 6 membered heteroaryl can be substituted with 1 to 4 substituents independently selected from the halogen group , difluoromethyl, trifluoromethyl, trideuterometyl, C₁₋₆ alkyl, C₃₋₇ cycloalkyl, oxo, hydroxyl, C₁₋₄-alkylcarbonyl, C₁₋₄-carbonyl alkoxy, aminocarbonyl and C₁₋₄-sulfonyl alkyl, wherein the C₁ alkyl ₋₆ and the cycloalkyl C₃₋₇, ₐ ₛᵘ ᵛₑᶻ, ₚᵘₑᵈₑₙ ₑₛₜₐʳ ₛᵘₛₜⁱₜᵘⁱᵈₒₛ ᶜₒₙ ₁ ₐ ₃ ᵍʳᵘₚₒ ᵈₑ ₕₐₗóᵍₑₙₒ, ᶜⁱₐₙₒ, ₜʳⁱᶠₗᵘₒʳₒₘₑₜⁱₗₒ, ᶜⁱᶜₗₒₐₗqᵘⁱₗₒ C₃₋₇, hydroxyl, C alco alkoxy and heterocycle 4 to 7 members, and in which two C₁₋₆ alkyl radicals attached to a carbon atom of the 5-7 membered heterocycle and the 5 or 6 membered heteroaryl, together with the carbon atom to which they are attached, can form a 3 to 6 member carbocycle; R²⁴ is halogen, C₁₋₄ alkyl or C₁₋₄ alkoxy; n is the number 0, 1, 2 or 3; and the salts, solvates and solvates of the salts thereof.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
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EP12167231 | 2012-05-09 |
Publications (1)
Publication Number | Publication Date |
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AR090994A1 true AR090994A1 (en) | 2014-12-30 |
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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ARP130101600A AR090994A1 (en) | 2012-05-09 | 2013-05-08 | BICYCLICALLY REPLACED URACILES AND USE OF THE SAME |
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UA112897C2 (en) * | 2012-05-09 | 2016-11-10 | Байєр Фарма Акцієнгезелльшафт | BICYCLIC SUBSTITUTED URATILES AND THEIR APPLICATIONS FOR THE TREATMENT AND / OR PREVENTION OF DISEASES |
JP2016535095A (en) * | 2013-11-08 | 2016-11-10 | バイエル ファーマ アクチエンゲゼルシャフト | Substituted 1,2,4-triazine-3,5-diones and their use as chymase inhibitors |
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CN105873919A (en) * | 2013-11-08 | 2016-08-17 | 拜耳医药股份有限公司 | Substituted uracils as chymase inhibitors |
EP3066098A1 (en) * | 2013-11-08 | 2016-09-14 | Bayer Pharma Aktiengesellschaft | Substituted uracils and use thereof |
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